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Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672. Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells.
Gene References into Functions
RNA-seq evidence of biallelic expression of BACE2 and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of BACE2 is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals. PMID: 27100087
Data identified two novel genome-wide significant associations: 2-h plasma glucose and HKDC1, and fasting C-peptide and BACE2. PMID: 23903356
BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. PMID: 23754390
BACE2 overexpression in cultured cells was found to lower net amyloid ss-protein levels. PMID: 22986058
The BACE2 distal promoter contains an activating cis-regulatory element that is responsive to Trichostatin A (TSA) treatment according to promoter reporter assays in HEK 293 cells. PMID: 20494980
All these data point to a role for BACE2 in the IRbeta trafficking and insulin signaling. In conclusion, BACE2 is hereby presented as an important enzyme in beta-cell function. PMID: 20943756
Trransgenic BACE2 mice show increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in the locus coeruleus. PMID: 19840121
BACE has a loose substrate specificity and that the substrate recognition site in BACE extends over several amino acids PMID: 11741910
Specificity and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity PMID: 12093293
the enzymatic properties of BACE2 were analyzed, including substrate specificity and pH range PMID: 12423367
A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer. ALP56 may be a useful target molecule in breast cancer treatment. PMID: 12611455
antagonistic effect with beta-site amyloid precursor protein-cleaving enzyme 1 on beta-amyloid peptide production in cells PMID: 12801932
Analysis revealed a 2.6-fold increase in BACE-2 mRNA levels in Down syndrome brains compared to the control group; increased secretion of BACE-2 by cultured fibroblasts and neural stem cells from Down syndrome patients was noted PMID: 12895444
Chromosome 21 BACE2 haplotype associates with Alzheimer's disease PMID: 16023140
the crystal structure of mature BACE2 in complex with a hydroxyethylamine transition-state mimetic inhibitor at 3.1 angstroms resolution was presented. PMID: 16305800
Data characterize the human beta-secretase 2 (BACE2) 5'-flanking region. PMID: 16757812
BACE2is not involved in the Alzheimer dissease(AD)pathogenesis of Down syndrome (DS) patients; instead, therapeutic interventions that potentiate BACE2 may prevent AD pathogenesis. PMID: 16816112
The expression levels of BACE2 was comparable between DS and controls in fetal brain and in adult brain. PMID: 18163181
study found no association between three BACE2 polymorphisms and sporadic Alzheimer's disease in the Chinese Han population even after statistical adjustment for age, gender and APOE epsilon 4 status PMID: 19124009
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Subcellular Location
Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Endoplasmic reticulum. Endosome.
Protein Families
Peptidase A1 family
Tissue Specificity
Brain. Present in neurons within the hippocampus, frontal cortex and temporal cortex (at protein level). Expressed at low levels in most peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach and trachea. Expressed